Estimation of Diabetic Retinal Microaneurysm Perfusion Parameters Based on Computational Fluid Dynamics Modeling of Adaptive Optics Scanning Laser Ophthalmoscopy

Abstract

Diabetic retinopathy (DR) is a leading cause of vision loss worldwide. Microaneurysms (MAs), which are abnormal outpouchings of the retinal vessels, are early and hallmark lesions of DR. The presence and severity of MAs are utilized to determine overall DR severity. In addition, MAs can directly contribute to retinal neural pathology by leaking fluid into the surrounding retina, causing abnormal central retinal thickening and thereby frequently leading to vision loss. Vascular perfusion parameters such as shear rate (SR) or wall shear stress (WSS) have been linked to blood clotting and endothelial cell dysfunction, respectively in non-retinal vasculature. However, despite the importance of MAs as a key aspect of diabetic retinal pathology, much remains unknown as to how structural characteristics of individual MAs are associated with these perfusion attributes. MA structural information obtained on high resolution adaptive optics scanning laser ophthalmoscopy (AOSLO) was utilized to estimate perfusion parameters through Computational Fluid Dynamics (CFD) analysis of the AOSLO images. The HemeLB flow solver was used to simulate steady-state and time-dependent fluid flow using both commodity hospital-based and high performance computing resources, depending on the degree of detail required in the simulations. Our results indicate that WSS is lowest in MA regions furthest away from the feeding vessels. Furthermore, areas of low SR are associated with clot location in saccular MAs. These findings suggest that morphology and CFD estimation of perfusion parameters may be useful tools for determining the likelihood of clot presence in individual diabetic MAs.

Predictive modelling of thrombus formation in diabetic retinal microaneurysms

“…Recent advances in imaging technology through AOSLO enable differentiating the thrombus-filled region from the perfused region in MAs. Bernabeu et al [ 27 ] reported that on AOSLO imaging thrombi are more frequently observed in saccular-shaped MAs compared to fusiform-shaped MAs.…”

“…Although retinal imaging now enables us to reconstruct the geometries of individual MAs and to perform computational fluid dynamics (CFD) studies to quantify the haemodynamic metrics, such as shear rate and wall shear stress [ 27 ], no computational studies have been performed to predict the initiation and formation of a thrombus in MAs. The ability to predict the course of thrombus development in MAs and thereby potentially better understand the overall risk of DR worsening might help ophthalmologists to monitor the progression of DR and guide appropriate timing for clinical intervention.…”

“…The white dotted line in (g) highlights the boundary of the MA3. ( f-g) are adopted from[27]. Simulation results of platelet aggregation in MA4 and comparison to the experimental observations.…”

Adaptive optics imaging of the retinal microvasculature

“…This allows the calculation of otherwise unmeasurable parameters such as wall shear stress and perfusion pressure. This information, if estimated accurately, would prove indispensable in deciding the likelihood that a given vessel or lesion will progress to lack of perfusion or development of other abnormalities . Such techniques can similarly be applied to study less severe structural abnormalities described above such as altered tortuosity or branching …”

“…This information, if estimated accurately, would prove indispensable in deciding the likelihood that a given vessel or lesion will progress to lack of perfusion or development of other abnormalities. 67,68 Such techniques can similarly be applied to study less severe structural abnormalities described above such as altered tortuosity or branching. 69 In addition to microaneurysms, AO can be used to image other characteristic pathologies with high resolution, such as neovascularisation, hard exudates, haemorrhages, cotton wool spots, and intraretinal cysts.…”